1fj1
From Proteopedia
(New page: 200px<br /> <applet load="1fj1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fj1, resolution 2.68Å" /> '''LYME DISEASE ANTIGE...) |
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| - | [[Image:1fj1.gif|left|200px]]<br /> | + | [[Image:1fj1.gif|left|200px]]<br /><applet load="1fj1" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1fj1" size=" | + | |
caption="1fj1, resolution 2.68Å" /> | caption="1fj1, resolution 2.68Å" /> | ||
'''LYME DISEASE ANTIGEN OSPA IN COMPLEX WITH NEUTRALIZING ANTIBODY FAB LA-2'''<br /> | '''LYME DISEASE ANTIGEN OSPA IN COMPLEX WITH NEUTRALIZING ANTIBODY FAB LA-2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Outer surface protein A (OspA) is a major lipoprotein of the Borrelia | + | Outer surface protein A (OspA) is a major lipoprotein of the Borrelia burgdorferi spirochete, the causative agent of Lyme disease. Vaccination with OspA generates an immune response that can prevent bacterial transmission to a mammalian host during the attachment of an infected tick. However, the protective capacity of immune sera cannot be predicted by measuring total anti-OspA antibody. The murine monoclonal antibody LA-2 defines an important protective B-cell epitope of OspA against which protective sera have strong levels of reactivity. We have now mapped the LA-2 epitope of OspA using both NMR chemical-shift perturbation measurements in solution and X-ray crystal structure determination. LA-2 recognizes the three surface-exposed loops of the C-terminal domain of OspA that are on the tip of the elongated molecule most distant from the lipid-modified N terminus. The structure suggests that the natural variation at OspA sequence position 208 in the first loop is a major limiting factor for antibody cross-reactivity between different Lyme disease-causing Borrelia strains. The unusual Fab-dominated lattice of the crystal also permits a rare view of antigen flexibility within an antigen:antibody complex. These results provide a rationale for improvements in OspA-based vaccines and suggest possible designs for more direct tests of antibody protective levels in vaccinated individuals. |
==About this Structure== | ==About this Structure== | ||
| - | 1FJ1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borrelia burgdorferi] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure | + | 1FJ1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borrelia burgdorferi] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry 2OSP. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FJ1 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Ding, W.]] | [[Category: Ding, W.]] | ||
| - | [[Category: Lawson, C | + | [[Category: Lawson, C L.]] |
[[Category: antibody fab fragment]] | [[Category: antibody fab fragment]] | ||
[[Category: lyme disease]] | [[Category: lyme disease]] | ||
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[[Category: ospa]] | [[Category: ospa]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:39:13 2008'' |
Revision as of 10:39, 21 February 2008
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LYME DISEASE ANTIGEN OSPA IN COMPLEX WITH NEUTRALIZING ANTIBODY FAB LA-2
Overview
Outer surface protein A (OspA) is a major lipoprotein of the Borrelia burgdorferi spirochete, the causative agent of Lyme disease. Vaccination with OspA generates an immune response that can prevent bacterial transmission to a mammalian host during the attachment of an infected tick. However, the protective capacity of immune sera cannot be predicted by measuring total anti-OspA antibody. The murine monoclonal antibody LA-2 defines an important protective B-cell epitope of OspA against which protective sera have strong levels of reactivity. We have now mapped the LA-2 epitope of OspA using both NMR chemical-shift perturbation measurements in solution and X-ray crystal structure determination. LA-2 recognizes the three surface-exposed loops of the C-terminal domain of OspA that are on the tip of the elongated molecule most distant from the lipid-modified N terminus. The structure suggests that the natural variation at OspA sequence position 208 in the first loop is a major limiting factor for antibody cross-reactivity between different Lyme disease-causing Borrelia strains. The unusual Fab-dominated lattice of the crystal also permits a rare view of antigen flexibility within an antigen:antibody complex. These results provide a rationale for improvements in OspA-based vaccines and suggest possible designs for more direct tests of antibody protective levels in vaccinated individuals.
About this Structure
1FJ1 is a Single protein structure of sequence from Borrelia burgdorferi and Mus musculus. This structure supersedes the now removed PDB entry 2OSP. Full crystallographic information is available from OCA.
Reference
Structural identification of a key protective B-cell epitope in Lyme disease antigen OspA., Ding W, Huang X, Yang X, Dunn JJ, Luft BJ, Koide S, Lawson CL, J Mol Biol. 2000 Oct 6;302(5):1153-64. PMID:11183781
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